A comparative study of free oligosaccharides in the milk of domestic animals

This study was conducted to provide a comprehensive analysis of the oligosaccharides in the milk of a variety of important domestic animals including cow, goat, sheep, pig, horse, and dromedary camel. Using an analytical workflow which included ultra-performance hydrophilic interaction liquid chromatography with fluorescence detection (UPLC-HILIC-FLD) and coupling to a quadrupole time of flight (qTOF) mass spectrometer (MS), detailed oligosaccharide libraries were established. The partial or full characterization of the neutral/fucosylated, phosphorylated and sialylated structures was facilitated by sequencing with linkage- and sugar- specific exoglycosidases. Relative peak quantification of the 2-AB labelled oligosaccharides provided additional information. Milks from domestic animals contained a much larger variety of complex oligosaccharides than was previously assumed and thirteen of these structures were previously identified in human milk. The direct comparison of the oligosaccharide mixtures could contribute to a better understanding of possible differences in their biological effects and highlight the potential value of animal milks for commercial oligosaccharide extraction.Fil: Albrecht, Simone. National Institute for Bioprocessing, Research and Training. NIBRT GlycoScience Group; IrlandaFil: Lane, Jonathan A.. Teagasc Food Research Centre; IrlandaFil: Mariño, Karina Valeria. National Institute for Bioprocessing, Research and Training. NIBRT GlycoScience Group; Irlanda. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Al Busadah, Khalid A.. King Faisal University. Camel Research Center; Arabia SauditaFil: Carrington, Stephen D.. University College Dublin. Veterinary Sciences Centre; IrlandaFil: Hickey, Rita M.. Teagasc Food Research Centre; IrlandaFil: Rudd, Pauline M.. National Institute for Bioprocessing, Research and Training. NIBRT GlycoScience Group; Irland

100 opportunities for more inclusive ocean research: cross-disciplinary research questions for sustainable ocean governance and management

In order to inform decision making and policy, research to address sustainability challenges requires cross-disciplinary approaches that are co-created with a wide and inclusive diversity of disciplines and stakeholders. As the UN Decade of Ocean Science for Sustainable Development approaches, it is therefore timely to take stock of the global range of cross-disciplinary questions to inform the development of policies to restore and sustain ocean health. We synthesized questions from major science and policy horizon scanning exercises, identifying 89 questions with relevance for ocean policy and governance. We then scanned the broad ocean science literature to examine issues potentially missed in the horizon scans and supplemented the horizon scan outcome with 11 additional questions. This resulted in an unprioritized list of 100 general questions that would require a cross-disciplinary approach to inform policy. The questions fell into broad categories including: coastal and marine environmental change, managing ocean activities, governance for sustainable oceans, ocean value, and technological and socio-economic innovation. Each question can be customized by ecosystem, region, scale, and socio-political context, and is intended to inspire discussions of salient cross-disciplinary research directions to direct scientific research that will inform policies. Governance and management responses to these questions will best be informed by drawing upon a diversity of natural and social sciences, local and traditional knowledge, and engagement of different sectors and stakeholders

Factors that influence clinicians’ decisions to offer intravenous alteplase in acute ischemic stroke patients with uncertain treatment indication:Results of a discrete choice experiment

Background: Treatment with intravenous alteplase for eligible patients with acute ischemic stroke is underused, with variation in treatment rates across the UK. This study sought to elucidate factors influencing variation in clinicians’ decision-making about this thrombolytic treatment. Methods: A discrete choice experiment using hypothetical patient vignettes framed around areas of clinical uncertainty was conducted with UK-based clinicians. Mixed logit regression analyses were conducted on the data. Results: A total of 138 clinicians completed the discrete choice experiment. Seven patient factors were individually predictive of increased likelihood of immediately offering IV alteplase (compared to reference levels in brackets): stroke onset time 2 h 30 min [50 min]; pre-stroke dependency mRS 3 [mRS 4]; systolic blood pressure 185 mm/Hg [140 mm/Hg]; stroke severity scores of NIHSS 5 without aphasia, NIHSS 14 and NIHSS 23 [NIHSS 2 without aphasia]; age 85 [68]; Afro-Caribbean [white]. Factors predictive of withholding treatment with IV alteplase were: age 95 [68]; stroke onset time of 4 h 15 min [50 min]; severe dementia [no memory problems]; SBP 200 mm/Hg [140 mm/Hg]. Three clinician-related factors were predictive of an increased likelihood of offering IV alteplase (perceived robustness of the evidence for IV alteplase; thrombolyzing more patients in the past 12 months; and high discomfort with uncertainty) and one with a decreased likelihood (high clinician comfort with treating patients outside the licensing criteria). Conclusions: Both patient- and clinician-related factors have a major influence on the use of alteplase to treat patients with acute ischemic stroke. Clinicians’ views of the evidence, comfort with uncertainty and treating patients outside the license criteria are important factors to address in programs that seek to reduce variation in care quality regarding treatment with IV alteplase. Further research is needed to further understand the differences in clinical decision-making about treating patients with acute ischemic stroke with IV alteplase

EST analysis in Ginkgo biloba: an assessment of conserved developmental regulators and gymnosperm specific genes

BACKGROUND: Ginkgo biloba L. is the only surviving member of one of the oldest living seed plant groups with medicinal, spiritual and horticultural importance worldwide. As an evolutionary relic, it displays many characters found in the early, extinct seed plants and extant cycads. To establish a molecular base to understand the evolution of seeds and pollen, we created a cDNA library and EST dataset from the reproductive structures of male (microsporangiate), female (megasporangiate), and vegetative organs (leaves) of Ginkgo biloba. RESULTS: RNA from newly emerged male and female reproductive organs and immature leaves was used to create three distinct cDNA libraries from which 6,434 ESTs were generated. These 6,434 ESTs from Ginkgo biloba were clustered into 3,830 unigenes. A comparison of our Ginkgo unigene set against the fully annotated genomes of rice and Arabidopsis, and all available ESTs in Genbank revealed that 256 Ginkgo unigenes match only genes among the gymnosperms and non-seed plants – many with multiple matches to genes in non-angiosperm plants. Conversely, another group of unigenes in Gingko had highly significant homology to transcription factors in angiosperms involved in development, including MADS box genes as well as post-transcriptional regulators. Several of the conserved developmental genes found in Ginkgo had top BLAST homology to cycad genes. We also note here the presence of ESTs in G. biloba similar to genes that to date have only been found in gymnosperms and an additional 22 Ginkgo genes common only to genes from cycads. CONCLUSION: Our analysis of an EST dataset from G. biloba revealed genes potentially unique to gymnosperms. Many of these genes showed homology to fully sequenced clones from our cycad EST dataset found in common only with gymnosperms. Other Ginkgo ESTs are similar to developmental regulators in higher plants. This work sets the stage for future studies on Ginkgo to better understand seed and pollen evolution, and to resolve the ambiguous phylogenetic relationship of G. biloba among the gymnosperms

Impact of centralising acute stroke services in English metropolitan areas on mortality and length of hospital stay: difference-in-differences analysis

Objective: To investigate whether centralisation of acute stroke services in two metropolitan areas of England was associated with changes in mortality and length of hospital stay. Design: Analysis of difference-in-differences between regions with patient level data from the hospital episode statistics database linked to mortality data supplied by the Office for National Statistics. Setting: Acute stroke services in Greater Manchester and London, England. Participants: 258 915 patients with stroke living in urban areas and admitted to hospital in January 2008 to March 2012. Interventions “Hub and spoke” model for acute stroke care. In London hyperacute care was provided to all patients with stroke. In Greater Manchester hyperacute care was provided to patients presenting within four hours of developing symptoms of stroke. Main outcome measures Mortality from any cause and at any place at 3, 30, and 90 days after hospital admission; length of hospital stay. Results: In London there was a significant decline in risk adjusted mortality at 3, 30, and 90 days after admission. At 90 days the absolute reduction was −1.1% (95% confidence interval −2.1 to −0.1; relative reduction 5%), indicating 168 fewer deaths (95% confidence interval 19 to 316) during the 21 month period after reconfiguration in London. In both areas there was a significant decline in risk adjusted length of hospital stay: −2.0 days in Greater Manchester (95% confidence interval −2.8 to −1.2; 9%) and −1.4 days in London (−2.3 to −0.5; 7%). Reductions in mortality and length of hospital stay were largely seen among patients with ischaemic stroke. Conclusions: A centralised model of acute stroke care, in which hyperacute care is provided to all patients with stroke across an entire metropolitan area, can reduce mortality and length of hospital stay

Gene expression and metabolite profiling of Populus euphratica growing in the Negev desert

BACKGROUND: Plants growing in their natural habitat represent a valuable resource for elucidating mechanisms of acclimation to environmental constraints. Populus euphratica is a salt-tolerant tree species growing in saline semi-arid areas. To identify genes involved in abiotic stress responses under natural conditions we constructed several normalized and subtracted cDNA libraries from control, stress-exposed and desert-grown P. euphratica trees. In addition, we identified several metabolites in desert-grown P. euphratica trees. RESULTS: About 14,000 expressed sequence tag (EST) sequences were obtained with a good representation of genes putatively involved in resistance and tolerance to salt and other abiotic stresses. A P. euphratica DNA microarray with a uni-gene set of ESTs representing approximately 6,340 different genes was constructed. The microarray was used to study gene expression in adult P. euphratica trees growing in the desert canyon of Ein Avdat in Israel. In parallel, 22 selected metabolites were profiled in the same trees. CONCLUSION: Of the obtained ESTs, 98% were found in the sequenced P. trichocarpa genome and 74% in other Populus EST collections. This implies that the P. euphratica genome does not contain different genes per se, but that regulation of gene expression might be different and that P. euphratica expresses a different set of genes that contribute to adaptation to saline growth conditions. Also, all of the five measured amino acids show increased levels in trees growing in the more saline soil

MHCII glycosylation modulates Bacteroides fragilis carbohydrate antigen presentation

N-linked glycans on class II MHC molecules are required for the presentation of glycoantigens, but not peptide antigens

Factors that influence variation in clinical decision-making about thrombolysis in the treatment of acute ischaemic stroke: results of a discrete choice experiment

Background: Intravenous thrombolysis for patients with acute ischaemic stroke is underused (only 80% of eligible patients receive it) and there is variation in its use across the UK. Previously, variation might have been explained by structural differences; however, continuing variation may reflect differences in clinical decision-making regarding the eligibility of patients for treatment. This variation in decision-making could lead to the underuse, or result in inappropriate use, of thrombolysis. Objectives: To identify the factors which contribute to variation in, and influence, clinicians’ decision-making about treating ischaemic stroke patients with intravenous thrombolysis. Methods: A discrete choice experiment (DCE) using hypothetical patient vignettes framed around areas of clinical uncertainty was conducted to better understand the influence of patient-related and clinician-related factors on clinical decision-making. An online DCE was developed following an iterative five-stage design process. UK-based clinicians involved in final decision-making about thrombolysis were invited to take part via national professional bodies of relevant medical specialties. Mixed-logit regression analyses were conducted. Results: A total of 138 clinicians responded and opted to offer thrombolysis in 31.4% of cases. Seven patient factors were individually predictive of the increased likelihood of offering thrombolysis (compared with reference levels in brackets): stroke onset time of 2 hours 30 minutes (50 minutes); pre-stroke dependency modified Rankin Scale score (mRS) of 3 (mRS4); systolic blood pressure (SBP) of 185 mmHg (140 mmHg); stroke severity scores of National Institutes of Health Stroke Scale (NIHSS) 5 without aphasia, NIHSS 14 and NIHSS 23 (NIHSS 2 without aphasia); age 85 years (65 years); and Afro-Caribbean (white). Factors predictive of not offering thrombolysis were age 95 years; stroke onset time of 4 hours 15 minutes; severe dementia (no memory problems); and SBP of 200 mmHg. Three clinician-related factors were predictive of an increased likelihood of offering thrombolysis (perceived robustness of the evidence for thrombolysis; thrombolysing more patients in the past 12 months; and high discomfort with uncertainty) and one factor was predictive of a decreased likelihood of offering treatment (clinicians’ being comfortable treating patients outside the licensing criteria). Limitations: We anticipated a sample size of 150–200. Nonetheless, the final sample of 138 is good considering that the total population of eligible UK clinicians is relatively small. Furthermore, data from the Royal College of Physicians suggest that our sample is representative of clinicians involved in decision-making about thrombolysis. Conclusions: There was considerable heterogeneity among respondents in thrombolysis decision-making, indicating that clinicians differ in their thresholds for treatment across a number of patient-related factors. Respondents were significantly more likely to treat 85-year-old patients than patients aged 68 years and this probably reflects acceptance of data from Third International Stroke Trial that report benefit for patients aged > 80 years. That respondents were more likely to offer thrombolysis to patients with severe stroke than to patients with mild stroke may indicate uncertainty/concern about the risk/benefit balance in treatment of minor stroke. Findings will be disseminated via peer-review publication and presentation at national/international conferences, and will be linked to training/continuing professional development (CPD) programmes. Future work: The nature of DCE design means that only a subset of potentially influential factors could be explored. Factors not explored in this study warrant future research. Training/CPD should address the impact of non-medical influences on decision-making using evidence-based strategies. Funding: The National Institute for Health Research Health Services and Delivery Research programme

A novel design process for selection of attributes for inclusion in discrete choice experiments: case study exploring variation in clinical decision-making about thrombolysis in the treatment of acute ischaemic stroke

A discrete choice experiment (DCE) is a method used to elicit participants’ preferences and the relative importance of different attributes and levels within a decision-making process. DCEs have become popular in healthcare; however, approaches to identify the attributes/levels influencing a decision of interest and to selection methods for their inclusion in a DCE are under-reported. Our objectives were: to explore the development process used to select/present attributes/levels from the identified range that may be influential; to describe a systematic and rigorous development process for design of a DCE in the context of thrombolytic therapy for acute stroke; and, to discuss the advantages of our five-stage approach to enhance current guidance for developing DCEs. A five-stage DCE development process was undertaken. Methods employed included literature review, qualitative analysis of interview and ethnographic data, expert panel discussions, a quantitative structured prioritisation (ranking) exercise and pilot testing of the DCE using a ‘think aloud’ approach. The five-stage process reported helped to reduce the list of 22 initial patient-related factors to a final set of nine variable factors and six fixed factors for inclusion in a testable DCE using a vignette model of presentation. In order for the data and conclusions generated by DCEs to be deemed valid, it is crucial that the methods of design and development are documented and reported. This paper has detailed a rigorous and systematic approach to DCE development which may be useful to researchers seeking to establish methods for reducing and prioritising attributes for inclusion in future DCEs.Financial support for this study was provided entirely by a grant from the National Institute for Health Research (NIHR) Health Services and Delivery Research Programme (project number: 12/5001/45)

Pericoronary and periaortic adipose tissue density are associated with inflammatory disease activity in Takayasu arteritis and atherosclerosis.

AimsTo examine pericoronary adipose tissue (PCAT) and periaortic adipose tissue (PAAT) density on coronary computed tomography angiography for assessing arterial inflammation in Takayasu arteritis (TAK) and atherosclerosis.Methods and resultsPCAT and PAAT density was measured in coronary (n = 1016) and aortic (n = 108) segments from 108 subjects [TAK + coronary artery disease (CAD), n = 36; TAK, n = 18; atherosclerotic CAD, n = 32; matched controls, n = 22]. Median PCAT and PAAT densities varied between groups (mPCAT: P P = 0.0002). PCAT density was 7.01 ± standard error of the mean (SEM) 1.78 Hounsfield Unit (HU) higher in coronary segments from TAK + CAD patients than stable CAD patients (P = 0.0002), and 8.20 ± SEM 2.04 HU higher in TAK patients without CAD than controls (P = 0.0001). mPCAT density was correlated with Indian Takayasu Clinical Activity Score (r = 0.43, P = 0.001) and C-reactive protein (r = 0.41, P P = 0.002). mPCAT density above -74 HU had 100% sensitivity and 95% specificity for differentiating active TAK from controls [area under the curve = 0.99 (95% confidence interval 0.97-1)]. The association of PCAT density and coronary arterial inflammation measured by 68Ga-DOTATATE positron emission tomography (PET) equated to an increase of 2.44 ± SEM 0.77 HU in PCAT density for each unit increase in 68Ga-DOTATATE maximum tissue-to-blood ratio (P = 0.002). These findings remained in multivariable sensitivity analyses adjusted for potential confounders.ConclusionsPCAT and PAAT density are higher in TAK than atherosclerotic CAD or controls and are associated with clinical, biochemical, and PET markers of inflammation. Owing to excellent diagnostic accuracy, PCAT density could be useful as a clinical adjunct for assessing disease activity in TAK